Solar radiation consists of a mixture of ultraviolet (UV) wavelengths including UVA wavelengths (about 315 nm to about 400 nm) and UVB wavelengths (about 280 nm to about 315 nm). Absorption of UV radiation by proteins and DNA increases toward the shorter wavelengths in the UVB range, as do the corresponding damaging effects of UV radiation to these molecules. UV-induced damage to DNA can give rise to neoplasia in UV-exposed tissues.
Neoplasia refers to the formation of one or more neoplasms. A neoplasm generally refers to an abnormal mass or colony of cells produced by a relatively autonomous new growth of tissue. Most neoplasms arise from the clonal expansion of a single cell that has undergone neoplastic transformation. Chemical, physical, or biological agents or events (e.g., exposure to UV radiation) can directly and irreversibly alter the genome of a cell, thereby transforming the cell to a neoplastic cell. Neoplastic cells are characterized by the loss of some specialized functions and the acquisition of new biological properties, foremost, the property of relatively uncontrolled growth. Cancer is a generic term for malignant neoplasms.
UV radiation can act as a complete carcinogen, i.e., capable, alone, of inducing neoplastic changes in cells. Alternatively, UV radiation can act as a co-carcinogen, acting in combination with one or more tumor initiators or promoters to induce neoplastic changes in cells.
The skin can be divided into two main layers: an outer layer—the epidermis—and the underlying dermis. The epidermis contains a basal germinative cell layer, proliferation of which provides cells for the continual renewal of the epidermis that is required as dead cells of the epidermal surface are sloughed off. While UV radiation can cause DNA damage to cells of both the dermis and the epidermis, the proliferative activity and high UV absorption of the epidermis can make the epidermis particularly susceptible to UV-related carcinogenesis.
UV radiation has been associated with various forms of epidermal damage including but not limited to erythema (sunburn) and DNA damage, which can lead to epidermal neoplasia. Various forms of epidermal neoplasia can be induced by UV radiation. For example, actinic keratosis (AK), pre-AK lesions, squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma can be induced by UV radiation.
Actinic keratosis is the most frequently observed form of UV-induced epidermal neoplasia. AK lesions are premalignant lesions considered to be either carcinoma in situ or squamous intraepidermal neoplasia. In humans, AK often occurs in those with fair skin and/or red hair, and those having substantial exposure to the sun early in life. Incidence of AK tends to increase with the age of the population being considered. The prevalence of AK tends to be higher in countries with high UV radiation and a fair-skinned population than in countries with a low level of UV radiation or a relatively dark-skinned population. If left untreated, AK can develop into SCC.
Melanoma and nonmelanoma skin cancers are among the most common types of cancer in Caucasian populations. Many epidemiological studies have demonstrated that the incidence of skin cancer has been increasing rapidly over the last decades.
Malignant melanoma is the most aggressive and life-threatening skin cancer. It develops in melanocytes—cells of the basal germinative cell layer of the epidermis that give the skin its color—and often spreads to other parts of the body. Incidence of malignant melanoma is closely associated with skin color and geography. Incidence among dark-skinned populations is about 1 per 100,000 population per year or less, but can be more than 50-fold greater among light-skinned populations in some areas of the world. The highest incidence rates have been reported in Queensland, Australia, with 56 new cases per 100,000 population per year for men and 43 new cases per 100,000 population per year for women. In the United States, incidence of melanoma has been estimated to be 14 new cases per year per 100,000 Caucasian men, and about 11 new cases per year per 100,000 Caucasian women.
Sun exposure, i.e., exposure to solar UV radiation, has been reported to be a general risk factor for melanoma. A more specific risk factor for melanoma is sun exposure during childhood, especially when the childhood history of exposure to solar UV radiation includes frequent or severe sunburn.
An additional risk factor for melanoma is skin type. Skin type I or II—skin that burns easily or severely and tans minimally or not at all—and the presence of multiple moles are important melanoma-related risk factors. Also, skin that is infrequently or only intermittently exposed to the sun (e.g., the skin of those who work indoors) may have a higher tendency to develop melanoma when intensely exposed to UV radiation than skin that is more regularly exposed to sunlight (e.g., the skin of those who work or are often outdoors).
Nonmelanoma skin cancers (NMSCs) constitute more than one-third of all cancers in the United States with an estimated incidence of over 600,000 cases per year. NMSCs are the most common malignancies occurring in the Caucasian population each year. Of these, most are basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs).
BCC represents 75% of NMSC and is the most common malignant disease throughout the world. There is an increased risk of NMSC in Caucasian populations, especially those who have blue eyes, a fair complexion, sunburn easily, suntan poorly, freckle with sun exposure, and/or have red, blond, or light-brown hair. NMSC is uncommon in blacks, Asians, and Hispanics. The incidence of NMSC is increasing rapidly in Caucasian populations of Europe, the United States, Canada, and Australia.
Chronic exposure to solar UV radiation is considered to be an important contributing factor to the development of NMSC. Over 80% of NMSCs occur on areas of the body that are frequently exposed to sunlight, such as the head, the neck, and the back of the hands. Additionally, BCC is also commonly found on the nose. The incidence of NMSC is elevated in individuals with a high cumulative exposure to UV light, such as those who work outdoors and those who more frequently participate in outdoor activities.
BCC is the most common skin cancer in humans. It often occurs on sun-exposed areas of the skin. It develops in the basal germinative cell layer of the epidermis. BCC can be very destructive and disfiguring, but rarely spread to other parts of the body.
SCC is a skin cancer arising from cells of the epidermis—the top layer of the skin—and can spread to other parts of the body. Squamous cell carcinoma occurs when abnormal cells—keratinocytes—of the epidermis migrate to and invade the underlying dermis.